Nanotopography-mediated reverse uptake platform for nucleic acid delivery and applications thereof

Abstract

This application discloses a nanotopography-mediated reverse uptake (NanoRU) platform useful for intracellular delivery of nucleic acids into mammalian cells, in particular stem cells, as well as methods of preparation and applications thereof. In particular, this system can be used to deliver small interfering ribonucleic acids (siRNAs) into neural stem cells and enhance neuronal differentiation of the stem cells.

The invention claimed is: 
     
       1. A nucleic acid delivery system comprising at least one nucleic acid, a self-assembled silicon oxide (silica) nanoparticle (SiNP) monolayer, and a film comprising one or more of extracellular matrix (ECM) proteins, wherein the silicon oxide nanoparticle monolayer is coated with the film, wherein:
 the film has topographical features capable of facilitating delivery of the at least one nucleic acid into cells; 
 the topographical features enable cellular uptake of the at least one nucleic acid without cellular uptake of the silicon oxide nanoparticle monolayer; and 
 the sizes of silica nanoparticles are in the range of 50 nm to 700 nm. 
 
     
     
       2. The nucleic acid delivery system of  claim 1 , wherein said silica nanoparticles (SiNPs) are assembled on a thin film of gold coated with a self-assembled monolayer (SAM) of a bifunctional organic compound. 
     
     
       3. The nucleic acid delivery system of  claim 2 , wherein said bifunctional organic compound comprises a thiol (—SH) end group and a carboxylic acid (—COOH) end group. 
     
     
       4. The nucleic acid delivery system of  claim 1 , wherein said one or more ECM proteins are independently selected from the group consisting of laminin, fibronectin, collagen, and combinations thereof. 
     
     
       5. The nucleic acid delivery system of  claim 1 , wherein said ECM protein is laminin. 
     
     
       6. The nucleic acid delivery system of  claim 1 , wherein the sizes of silica nanoparticles are in the range of 100 nm to 300 nm. 
     
     
       7. The nucleic acid delivery system of  claim 1 , wherein said nucleic acid is a small interfering ribonucleic acid (siRNA). 
     
     
       8. The nucleic acid delivery system of  claim 1 , wherein said cells are mammalian cells. 
     
     
       9. The nucleic acid delivery system of  claim 1 , wherein said cells are astrocytes or cancer cells. 
     
     
       10. The nucleic acid delivery system of  claim 1 , wherein said cells are stem cells. 
     
     
       11. The nucleic acid delivery system of  claim 1 , wherein said cells are neural stem cells (NSCs). 
     
     
       12. A nucleic acid delivery kit comprising a nucleic acid delivery platform of  claim 1 .